Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 5 uppsatser. Även tryckt utgåva.

Nitric oxide (NO) is an important regulator of pulmonary blood flow and attenuates hypoxic pulmonary vasoconstriction (HPV). Nitric oxide is synthesized enzymatically in a number of tissues, including the lungs, and can also be generated from reduction of nitrite during hypoxia and acidosis. Inhaled nitric oxide (INO) is a selective pulmonary vasodilator, with no effects on systemic arterial blood pressure due to inactivation by hemoglobin in the blood. INO has distant effects both within the lungs and in other organs, since NO can be transported to remote tissues bound to proteins, or as more stable molecules of nitrite and nitrate. In healthy pigs, INO causes vasoconstriction and down regulation of endogenous NO production in lung regions not reached by INO, and predominantly so in hypoxic lung regions, i.e. augmentation of HPV. In this thesis, distant effects of INO in pigs with endotoxemic- and lavage-induced lung injuries were studied. INO increased the NO production in lung regions not reached by INO in endotoxemic pigs, whereas endogenous NO production was unaffected in pigs with lavage-induced injury. Metabolic and/or hypercapnic acidosis frequently occurs in critically ill patients, but whether acidosis affects the endogenous pulmonary NO production is unclear. The regional NO production and blood flow in hyperoxic and hypoxic lung regions, were studied during metabolic and hypercapnic acidosis. Neither metabolic, nor hypercapnic acidosis changed the endogenous NO production in hyperoxic or hypoxic lung regions. Metabolic acidosis potentiated HPV, whereas hypercapnic acidosis transiently attenuated HPV. In conclusion, the present thesis has demonstrated that INO in experimental sepsis increases the endogenous NO production in lung regions not reached by INO, which may cause increased shunt and poor response to INO. This distant effect is not seen in lavage injuried lungs, an experimental model with less inflammation. Acidosis does not affect the endogenous pulmonary NO production in hyperoxic or hypoxic lung regions. Whereas metabolic acidosis potentiates HPV, hypercapnic acidosis transiently attenuates HPV, due to a combination of hypercapnia-induced increase in cardiac output and a probable vasodilating effect of the CO2-molecule.

Diss. (sammanfattning) Umeå : Univ., 2008. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Thesis (M.S.)--Uniformed Services University of the Health Sciences, 2005. / Typescript (photocopy).

Active Particles at the Temelin NPP, Radiobiological Risks and Protective Precautions The term active particle (AC) was applied on Temelín NPP (ETE) in order to denominate small fragments of high radioactive matters, sized up to 1 millimeter, forming into primary circuit. In accordance with latest available know-how, the ACs major contains corrosion products, that were activated during passing through reactor core. After primary circuit opening, due to carry out outage works, the ACs will spread into ETE radiation controlled area. In proportion to their size, the ACs activity is relative high, so that the ACs can jeopard workers, who will contact them. This jeopardy is namely associated with AC penetration into organism - ingestion or inhalation. The main goal of this dissertation is to determine grounds of ACs occurence in Temelín NPP, to review ACs radiobiological risks and to evaluate procedures and protective aids, used for assurance of workers radiation protection. This dissertation is resuming actual know-how about ACs occured and occuring in Temelín NPP, including suggestions for radiation protection procedures and for protective aids utilization, that are to be used for reduction of above mentioned jeopardy. Next areas are concerned: - analysis of ACs forming and matters composition - description of ACs physical-radiation parameters - identification of main ACs sources in primary circuit - assesment and evaluation of radiobiological jeopardies, associated with ACs occurence in Temelín NPP radiation controlled area - assesment of procedures and protective aids used for protection of workers, who can be endangered by ACs

Made available in DSpace on 2014-06-11T19:31:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-11-28Bitstream added on 2014-06-13T20:41:23Z : No. of bitstreams: 1 almeida_rm_dr_jabo.pdf: 437070 bytes, checksum: e5cd6f576c7b9ff4974078130d3e9da5 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A administração intravenosa de anestésicos voláteis halogenados pode ser considerada uma alternativa à aplicação pela via inalatória, e neste contexto, as formulações emulsificadas têm mostrado segurança, eficiência e bons planos anestésicos. Neste estudo, objetivou-se comparar os efeitos hemodinâmicos e respiratórios das administrações intravenosa e inalatória de isofluorano em cães, após a determinação da taxa de infusão intravenosa de 6,99 mL/kg/h deste halogenado em emulsão lipídica. Para tanto, foram utilizados oito cães, os quais formaram três grupos distintos: grupo IV – anestesia intravenosa por infusão de emulsão lipídica com isofluorano; grupo E - anestesia inalatória com isofluorano, associada à infusão intravenosa de emulsão lipídica sem o halogenado; e grupo IN - anestesia inalatória com isofluorano, associada à infusão intravenosa de solução de NaCl 0,9%. Foram evidenciadas diminuições da contratilidade cardíaca, índice cardíaco e pressão arterial sistêmica a partir de 10 e 40 minutos de anestesia, respectivamente, nos grupos IV e E. A hipotensão no grupo IV resultou em acidose metabólica, porém, hipoxemia não foi observada. O grupo IN apresentou manutenção do índice cardíaco, apesar de reduções do índice de resistência vascular sistêmica e pressão arterial. A taxa de infusão intravenosa determinada foi efetiva na manutenção de plano de anestesia cirúrgica em cães. As infusões intravenosas de isofluorano e emulsão lipídica causaram depressão cardíaca e hipotensão. Em relação à função respiratória, nenhum dos grupos mostrou efeitos deletérios. / The intravenous administration of halogenated anesthetics can be considered an alternative to the application by the inhalation route, moreover, emulsified formulations have been showing safety, efficiency and appropriated anesthetic depth. The aim of this study was to compare the effects of isoflurane anesthesia by intravenous or inhalational route on hemodynamic and respiratory variables, after the determination of the intravenous infusion rate of 6.99 mL/kg/h of this anesthetic in lipid emulsion, in dogs. Therefore, eight dogs were distributed in three different protocols: IV group – intravenous anesthesia with emulsified isoflurane; E group – inhalational anesthesia with isoflurane associated to intravenous infusion of lipid emulsion; and IN group - inhalational anesthesia with isoflurane associated to intravenous infusion of 0.9% NaCl solution. The results regarding IV and EM groups revealed decreases of heart contractility, cardiac index and systemic blood pressure starting from 10 and 40 minutes of anesthesia, respectively. The hypotension in the IV group resulted in metabolic acidosis, however, hypoxemia was not observed. The IN group demonstrated maintenance of cardiac index, despite of reduction of the blood pressure and systemic vascular resistance index. The intravenous infusion rate determined was effective in the maintenance of an anesthetic depth of general anesthesia in dogs. The intravenous infusions of isoflurane and lipid emulsion caused cardiac depression and hypotension. In relation to respiratory function, the inhalational route and the intravenous infusions of isoflurane and lipid emulsion did not result in harmful effects.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The aim of this study was to evaluate acute and subacute renal and hepatic toxicity of the oral administration of tepoxalin in cats submitted to hypotension with isoflurane. Eighteen adult male mongrel cats were used in this study, weighing between 3 and 5 kg and clinically healthy. The animals were divided into three groups, which were anesthetized and submitted to hypotension with isoflurane (CON), or which, in addition, tepoxalin was administered two hours prior to the hypotension procedure (PRE) or after the hypotension procedure (POS). The animals from groups PRE and POS also received the same doses of tepoxalin every 24 hours, during the five days following the procedure. In order to achieve a condition of moderate hypotension, animals were induced and maintained with isoflurane in variable concentration, for maintenance of mean arterial pressure (MAP) between 45 and 60 mmHg, during 60 minutes. Complete blood count and serum concentrations of alanine aminotransferase (ALT), alkaline phosphatase (FA) and urea (U) were evaluated at baseline and 24 hours, 48 hours and 7 days after hypotension. Serum concentration of creatinine (Cr), fractional excretion of sodium (FENa) and urinary concentrations of Cr, gamma-glutamyl transferase (GGT), proteinuria and albuminuria were evaluated at baseline and 24 hours, 48 hours and 7 days after hypotension. The model chosen was efficient in maintaining the proposed condition of hypotension. No physiological changes were observed in complete blood count, serum biochemistry profile (ALT, FA, U and Cr), FENa and urinary GGT. An increase in urine protein-creatinine ratio was observed in CON and PRE at 24 and 48 hours after hypotension. Urine albumin-creatinine ratio showed increase in CON at 24 hours and maintained elevated values with regard to the other groups until 7 days after hypotension. The authors conclude that administration of tepoxalin does not cause changes in hepatic parameters, urea, creatinine, fractional excretion of sodium and urinary GGT in cats submitted to anesthetic hypotension. However, there is a risk of mild renal injury by administering the drug prior to the hypotensive procedure. / Este estudo objetivou avaliar a toxicidade renal e hepática, aguda e subaguda, da administração oral da tepoxalina em gatos submetidos à hipotensão com isofluorano. Foram utilizados 18 gatos, machos, adultos, sem raça definida, com peso entre 3 e 5 kg e comprovadamente hígidos. Os animais foram alocados em três grupos, os quais foram anestesiados e submetidos à hipotensão com isofluorano (CON), ou que ainda receberam tepoxalina duas horas antes do procedimento de hipotensão (PRÉ) ou após a recuperação anestésica do procedimento de hipotensão (PÓS). Os animais dos grupos PRÉ e PÓS também receberam as mesmas doses de tepoxalina a cada 24 horas, durante cinco dias pós procedimento. Para a caracterização de um quadro de hipotensão moderada, os animais foram induzidos e mantidos anestesiados com isofluorano em vaporização variável, para a manutenção da pressão arterial média (PAM) entre 45 e 60 mmHg durante 60 minutos. Foram avaliados hemograma e concentrações séricas de alanina amino-transferase (ALT), fosfatase alcalina (FA) e ureia (U) no período basal e 24 horas, 48 horas e 7 dias após a hipotensão. A concentração sérica de creatinina (Cr), a fração de excreção de sódio (FENa) e as concentrações urinárias de Cr, gama-glutamiltransferase (GGT), proteínas totais e albumina foram avaliadas no momento basal e 24 horas, 48 horas e 7 dias após a hipotensão. O modelo escolhido foi eficiente na manutenção do quadro de hipotensão proposto. Não foram observadas alterações fisiológicas no hemograma, bioquímica sérica (ALT, FA, U e Cr), FENa e na GGT urinária. Observou-se elevação estatística na razão proteína-creatinina na urina no CON e no PRÉ em relação ao PÓS às 24 e às 48 horas de avaliação. A razão albumina-creatinina na urina apresentou elevação estatística no CON em relação aos demais à partir das 24 horas de avaliação, mantendo essa elevação até os 7 dias de avaliação. Concluiuse que a administração de tepoxalina não causou alterações de parâmetros hepáticos, ureia, creatinina, FENa e GGT urinária em gatos submetidos à hipotensão anestésica, entretanto há o risco de ocorrência de injúria renal discreta devido à proteinúria observada no grupo em que a tepoxalina foi administrada antes do procedimento hipotensor.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / This study aimed to evaluate the possible renal and hepatic toxicities, acute and subacute, of the administration of tepoxalin in dogs submitted to hypotension with isoflurane. A total of 12 dogs were used, which received 10 mg kg-1 of tepoxalin PO two hours before induction of hypotension (T) or were only submitted to hypotension with isoflurane (C). For the subacute study, animals in T were treated with tepoxalin during 5 days, following the hypotensive procedure. The dogs were submitted to hypotension (MAP= 50-60mmHg) for isoflurane in a circular circuit valve, with adjusted FR for the ETCO2 remained between 35-45mmHg. ToC was maintained between 37 and 38oC. HR, SAP, MAP, DAP, CVP, ETCO2 and ETIso were evaluated at 0, 10 and every 10 min up to 60min of hipotension. pH, PaO2, PaCO2, SaO2, HCO3-, BD, Na+, K+, Ca2+ and bleeding time evaluations were carried out before hypotension and at 30 and 60min of hipotension. For renal and hepatic evaluation, serum levels of U, Cr, ALT, alkaline phosphatase, GGT and urinary levels of GGT, Cr and GGT:Cr ratio were determined at 12h, 24h and seven days after the procedure. During the anesthetic procedure, only CVP presented elevation in relation to 0min in both groups at 50 and 60min of evaluation. In blood gas and electrolyte measurement, only Na+ presented levels below to basal at 60min in T, and this same group showed increased values at all intervals, in comparison between groups. Moreover, bleeding time was shown to be more elevated at 30min of evaluation in animals in T, when compared to the ones in C. The variables corresponding to creatinine depuration, GGT:Cr ratio and UV remained stable during the evaluations; however, urinary GGT levels presented increased values in animals in C when compared to T, at 60min of evaluation. At this same interval, urinary Cr values were elevated in T. Serum levels of ALT, alkaline phosphatase, U and Cr presented minor alterations, remaining within reference values; however, GGT presented increased values at 60min of evaluation, when compared to 0min. On the seventh day of evaluation, a reduction in leukocyte number was observed in animals in T, when compared to C. Side effects were not observed in both groups. The prior administration of tepoxalin in healthy dogs submitted to hypotension did not cause significant effects upon renal and hepatic functions. Moreover, daily administrations during five days, following the anesthetic procedure, did not alter the functions of the organs mentioned. Therefore, tepoxalin showed to be a safe NSAID to be used in healthy dogs, submitted to hypotension during anesthesia with isoflurane. / Objetivou-se avaliar as possíveis toxicidades renal e hepática, aguda e subaguda, da administração de tepoxalina em cães submetidos à hipotensão com isofluorano. Foram utilizados 12 cães, os quais receberam 10mg kg-1 de tepoxalina VO duas horas antes da indução da hipotensão (T) ou somente foram submetidos à hipotensão com isofluorano (C). Para o estudo subagudo, os animais do T foram tratados com tepoxalina, durante cinco dias, seguidos ao procedimento hipotensor. Os cães foram submetidos à hipotensão (PAM = 50-60mmHg) por isofluorano em circuito circular valvular, com FR ajustada para que o ETCO2 permanecesse entre 35-45mmHg. A TºC foi mantida entre 37 e 38ºC. Avaliaram-se FC, PAS, PAM, PAD, PVC, ETCO2, e ETIso em 0, 10 e a cada 10min até 60min da hipotensão. As avaliações de pH, PaO2, PaCO2, SaO2, HCO3-, DB, Na+, K+ e Ca2+ e tempo de sangramento foram realizadas antes da hipotensão e aos 30 e 60min da hipotensão. Para a avaliação renal e hepática foram determinados os níveis séricos de U, Cr, ALT, FA, GGT e os níveis urinários de GGT, Cr e a proporção GGT:Cr em 12h, 24h e sete dias após o procedimento. Durante o procedimento anestésico somente a PVC apresentou elevação em relação aos 0min, em ambos os grupos aos 50 e 60min de avaliação. Na mensuração dos gases sanguíneos e eletrólitos, apenas o Na+ demonstrou níveis menores que o basal aos 60min no T, e este mesmo grupo apresentou valores aumentados em todos os momentos, na comparação entre os grupos. Ainda, o tempo de sangramento foi maior aos 30min de avaliação, nos animais do T, quando comparado aos do C. As variáveis correspondentes à depuração da creatinina, razão GGT:Cr e DU permaneceram estáveis durante as avaliações, porém, os níveis de GGT urinária apresentaram valores aumentados nos animais do C, quando comparados ao T, aos 60min de avaliação. Nesse mesmo momento, os valores de Cr urinária estavam aumentados dentro do T. Os níveis séricos de ALT, FA, U e Cr apresentaram poucas alterações, permanecendo dentro dos limites de referência, porém, a GGT apresentou valores aumentados aos 60min de avaliação, comparando-se com 0min. No sétimo dia de avaliação, observou-se redução do número de leucócitos nos animais do T, quando comparados aos do C. Não foram observados efeitos colaterais em ambos os grupos. A administração prévia de tepoxalina em cães hígidos submetidos à hipotensão, não ocasionou efeitos significativos sobre as funções renal e hepática dos mesmos. Da mesma forma, administrações diárias durante cinco dias, seguidas ao procedimento anestésico, não alteraram as funções dos referidos órgãos. Portanto, a tepoxalina demonstrou ser um AINE seguro para utilização em cães hígidos, submetidos à hipotensão durante anestesia com isofluorano.

Made available in DSpace on 2014-10-09T12:35:58Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:59:50Z (GMT). No. of bitstreams: 0 / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP